This invention is related to methods for improving the healing rate of infected wounds or sores on humans or animals, that are otherwise slow to heal, by usual treatment methods. More specifically, the present invention is related to a mixture of surfactants and their use in removing biofilms, especially those from body tissue or materials in contact with body tissue such as implants.
The historical view of bacteria is that they are free-living organisms easily kept in check by antibiotics, however, scientists are now realizing that bacteria spend most of their lives in colonies, or biofilms, even in the human body. Biofilms are communities of bacteria in self-produced slime and may be found almost anywhere that solids and liquids meet, whether in nature, in hospitals or in industrial settings. According to the United States' Centers for Disease Control, biofilms are implicated in more than 80% of chronic inflammatory and infectious diseases caused by bacteria, including ear infections, gastrointestinal ulcers, urinary tract infections and pulmonary infections in cystic fibrosis patients. It is widely thought that in their natural habitat most bacteria live as a community and attach to surfaces as biofilms and that many infections in humans are related to biofilms. While single bacteria may be treatable with antibiotics, the films can be 1,000 times more resistant and most can only be removed surgically.
Bacteria that form biofilms occasionally infect implants such as pacemakers, stents, and artificial joints. These biofilm sites periodically shed bacteria, often referred to in the art as adventurers, which can ignite acute infections and fever. While antibiotics can knock out these free-swimming bacteria and temporally calm down the infection, the biofilm remains untouched. The only permanent solution is removal of the biofilm-coated device and replacement with a new sterilized implant.
A permanent bacterial biofilm in the sinuses can ignite an immune response leading to chronic sinus infections, with symptoms including fever and cold-like symptoms. So far, the most effective treatment is to surgically remove the affected tissue.
Bacteria also form permanent, mostly lifelong, biofilms in the mucus-filled lungs of cystic fibrosis patients and are responsible for the chronic lung infections that lead to early death. Although long-lasting antibiotic treatment helps, it cannot eradicate the infection completely.
Biofilms are difficult to eradicate with conventional antimicrobial treatments since they are far more resistant to antibiotics than planktonic, or free-floating adventurer cells. Biofilms also pose a persistent problem in many industrial processes, including drinking water distribution networks and manufacturing environments.
The problem with a chronic infection is that the immune system attempts to clear the infection but is unable to. The longer the chronic infection goes on, the more damage there will be to tissue at the site of the infection because the immune response often involves the release of toxic compounds that have no effect on biofilms but can damage the surrounding tissues.
In one reported observation, over a period of about six hours, a single bacterium laid down a glue to attach itself to a surface, then divided into daughter cells, making certain to cement each daughter to itself before splitting in two. The daughters continued to divide until they formed a cluster, like a brick and mortar building, at which point the bacteria secreted a protein encasing the cluster like the shell of a building. The clusters are separated by micro-channels that may allow nutrients in and waste out.
Bed sores, also known as pressure ulcers, pressure sores, or decubitus ulcers are skin lesions which can be caused by friction, humidity, temperature, incontinence, medication, shearing forces, age and unrelieved pressure. Any part of the body may be affected, however, bony or cartilaginous areas, such as the elbows, knees, ankles and sacrum are most commonly affected. If discovered early, bedsores are treatable. However, they may sometimes be fatal. According to health authorities in the UK and USA, bedsores are the second iatrogenic cause of death, after adverse drug reactions causing hospitals to spend about $5 billion annually for treatment of pressure ulcers.
Biofilms are one of the most common reasons for delayed healing in pressure ulcers. Biofilm formation occurs rapidly in wounds and stalls healing by keeping the wound inflamed. Frequent debridement and antimicrobial dressings are needed to control the biofilm. Infection prevents healing of pressure ulcers. Symptoms of infection in a pressure ulcer include slow or stalled healing and pale granulation tissue. Infection can expand from local to systemic. Symptoms of systemic infection include fever, pain, redness, swelling, warmth of the area, and purulent discharge. Additionally, infected wounds may have a gangrenous smell, be discolored, and may eventually exude even more pus. In order to eliminate this problem, it is imperative to apply antiseptics at once. Hydrogen peroxide, a near-universal toxin, is not recommended for this task as it increases inflammation and impedes healing. Systemic antibiotics are not recommended in treating local infection in a pressure ulcer, as it can lead to bacterial resistance. They are only recommended if there is evidence of advancing cellulitis, osteomyelitis, or bacteremia.
Surfactants with detergency are known to remove a number of water insoluble materials from hard surfaces such as oily materials, grassy materials, proteinaceous materials and dirt based materials. Surfactants are usually organic compounds that are amphiphilic, meaning they contain both hydrophobic moieties, often referred to as their tails, and hydrophilic moieties, often referred to as their heads. Surfactants will diffuse into water and adsorb at interfaces between air and water or at the interface between oil and water, in the case where water is mixed with oil. The water-insoluble hydrophobic group may extend out of the bulk water phase, into the air or into the oil phase, while the water-soluble head group remains in the water phase.
Detergents have also been used to decellularise organs with limited success. This process maintains a matrix of proteins that preserves the structure of the organ and often the microvascular network. The process has been successfully used to prepare organs such as the liver and heart for transplant in rats. Pulmonary surfactants are also naturally secreted by type II cells of the lung alveoli in mammals.
Other approaches toward treating biofilms are known. U.S. Pat. No. 8,753,662 teaches methods of inhibiting biofilm formation or reducing biofilms in a subject or on a device or surface by administering a charged compound such as a polyamino acid to a subject, device or surface. The invention also relates to compositions for inhibiting biofilm formation or reducing biofilms. U.S. Pat. No. 8,748,617 discloses the use of amide compounds or salts thereof and biofilm inhibitor, biofilm remover, and disinfectant containing the same. The disclosure provides an amide compound and salt thereof that is capable of inhibiting biofilm formation or removing deposited biofilms. U.S. Pat. No. 8,747,872 relates to methods and compositions for treating pulmonary infection. In particular, it provides nanoemulsion compositions and methods of using the same to treat bacteria associated with biofilms such as those found in pulmonary infections. Compositions and methods of the invention find use in, among other things, clinical settings for use as therapeutic and preventative medicine, industrial applications, and research applications.
The prior art cited above shows materials designed to kill bacteria or inhibit biofilm formation. It also shows that certain detergent surfactants are known to lyse cell membranes and tissues by disorganizing the membrane's lipidic bilayer, which would damage healthy tissue, however, they are marginally effective. The milder detergents disclosed in the art such as octyl thioglucoside, octyl glucoside or dodecyl maltoside that are used to solubilize membrane proteins such as enzymes and receptors without denaturing them are expensive and not widely available.
It is clear that there is a need for an effective method to remove bacterial biofilms, especially those in bedsores or on implants, to reduce the mortality rate due to infections, both internal and external to the body. Further, a method that avoids systemic antibiotics would have advantages of lower treatment cost, the avoidance of adverse reactions to the medications, and avoid the development of bacterial resistance to antibiotics. A nonsurgical method to remove biofilms would likely have lower treatment costs, reduced risk of complications, and reduced need to remove healthy tissue along with the infected tissue.
In spite of the ongoing effort there is still a desire for a method of disrupting biofilms thereby releasing the bacteria therefrom to allow natural mitigation of infection or increased access to systemic or localized antibiotics. Such an improvement is provided herein.